Glioblastoma Treatment with Temozolomide and Bevacizumab and Overall Survival in a Rural Tertiary Healthcare Practice

Abstract

Background The efficacy of temozolomide (TMZ) chemotherapy for treating newly diagnosed glioblastoma (GBM), a primary brain tumor with short survival, was demonstrated in a clinical trial in 2005, and since then, the standard-of-care for newly diagnosed GBM has been maximal safe surgery followed by 60 Gray of radiation with concomitant and adjuvant TMZ (standard radiotherapy and TMZ). In 2009, clinical trials also reported on the efficacy of bevacizumab for treating recurrent GBM. We performed a retrospective cohort study to evaluate the impact of treatment regimens on overall survival for patients with GBM at a rural tertiary healthcare practice. Methods We retrospectively reviewed the medical records of 307 consecutive, newly diagnosed GBM patients at one institution between 1995 and 2012 and assessed treatment patterns. We also compared overall survival according to the treatment received. Results Only 0.6% (1/163) of patients diagnosed before 2005 received standard radiotherapy and TMZ versus 36.1% (52/144) of patients diagnosed since 2005 (P < 0.0001). For patients who received standard radiotherapy and TMZ, the median overall survival was 17.0 months versus 7.0 months for patients who received 60 Gray of radiation but no chemotherapy (P = 0.0000078). The median overall survival was 15.4 months in the 19 patients treated with bevacizumab monotherapy at first GBM recurrence versus 6.8 months in the 32 patients with no treatment at first GBM recurrence (P = 0.00015), but patients who received bevacizumab were younger and more likely to have had a surgical resection and 60 Gray of radiation at diagnosis. Conclusions TMZ and bevacizumab therapies were rapidly adopted in a rural tertiary healthcare setting, and patients who received these treatments had increased overall survival. However, advantageous prognostic factors in patients who received bevacizumab at recurrence may have influenced the extent of the increase in overall survival attributed to this treatment.

Surgery, Octreotide, Temozolomide, Bevacizumab, Radiotherapy, and Pegvisomant Treatment of an AIP Mutation‒Positive Child

“…VEGF staining is present in somatotroph adenomas, and we have not seen a difference between AIP mutation‒positive and AIP mutation‒negative cases (17). Both treatments were started with the hope of achieving additive or augmented effects, as data from patients with glioblastoma multiforme showed the combination of these two drugs causing remarkable tumor reduction along with survival benefits [(18) and ClinicalTrials.gov Identifier: NCT00612339, phase II, 2008]. Recently, temozolomide and bevacizumab treatment was stopped, as no further benefit was seen.…”

Disentangling the therapeutic tactics in GBM: From bench to bedside and beyond

“…Having approved by the FDA in 2009, Bev has been employed either alone or in combination with TMZ in the treatment of both primary and recurrent GBM (Blumenthal et al, 2015). Preclinically, the antitumorigenic activity of Bev, in an intracranial GBM xenograft animal model derived from patient tumor spheroids showed a strong decrease in tumor growth, along with a significant reduction of vascular supply to the cells (Carter et al, 2018). The minimum steady‐state concentration of Bev was determined in a phase II clinical trial employing 69 patients, wherein 7.5 mg/kg every 3 weeks or 5 mg/kg every 2 weeks was found to be similar (Gaudreault et al, 2004).…”

“…The median PFS rates in Post-Bev cohorts were found to be two months longer than that of Pre-Bev cohorts, indicating possible benefits of this drug in GBM treatment (Johnson et al, 2018). Another retrospective study was carried out, which reported that 307 patients with newly diagnosed GBM on treatment with TMZ and Bev have shown the increased progression of free survival rates of about 15.4 months (Carter et al, 2018). tumor suppressor gene (Janku et al, 2014).…”

Molecular and Cellular Complexity of Glioma. Focus on Tumour Microenvironment and the Use of Molecular and Imaging Biomarkers to Overcome Treatment Resistance

“…The standard therapy relies on the Stupp protocol, officially proposed in 2005 [3,4]. The Stupp protocol is based on tumour surgical resection, followed by postoperative radiotherapy (RT), 60 Gy/30 fractions as standard, and concomitant plus adjuvant Temozolomide (TMZ) treatment [5]. Despite an increase in overall survival, the prognosis remains poor because of the development of GBM resistance to TMZ [6].…”